Foundations · Year 1 · from Foundations
Case 3: Amanita Phalloides Poisoning (RNA Polymerase II Inhibition)
Clinical Image
Source: Wikipedia - Amanita phalloides - CC BY-SA 3.0
Case Presentation
A 45-year-old man presents to the emergency department with severe abdominal pain, profuse watery diarrhea, and vomiting 10 hours after eating wild mushrooms he foraged. He initially felt fine after the meal but symptoms began 6 hours later. On examination, he appears ill with dry mucous membranes and tachycardia. Initial labs show mild elevation of AST and ALT. He is admitted for supportive care. Over the next 48 hours, his liver enzymes rise dramatically (AST 8,500, ALT 6,200), coagulopathy develops (INR 4.2), and he becomes encephalopathic. Toxicology consultation identifies this as Amanita phalloides (death cap mushroom) poisoning. The mushroom contains alpha-amanitin, a cyclic peptide that potently inhibits RNA polymerase II by binding to the enzyme and blocking translocation during elongation. Without mRNA synthesis, hepatocytes cannot produce essential proteins and undergo massive necrosis. He is treated with N-acetylcysteine, high-dose penicillin (which may compete with alpha-amanitin for hepatocyte uptake), and silibinin (milk thistle extract). Despite supportive care, he develops fulminant hepatic failure requiring emergency liver transplantation. The delayed symptom onset (6-12 hours) is characteristic and often leads to initial misdiagnosis.
Key Learning Points
- Alpha-amanitin from Amanita phalloides specifically inhibits RNA polymerase II, blocking mRNA synthesis; this halts production of essential proteins in all cells, with hepatocytes being particularly vulnerable due to their high transcriptional activity
- RNA Pol II is responsible for transcribing all protein-coding genes; its inhibition is rapidly lethal to metabolically active cells
- The characteristic delayed onset (6-12 hours) distinguishes Amanita poisoning from other mushroom toxicities; by the time GI symptoms appear, significant hepatotoxin absorption has occurred